| ObjectiveMajor depression (MD) is a common mood disorder, and has large heterogeneity on the etiology and clinical features. Clinical studies revealed that some depressive symptoms such as relief of patients with MD could be remitted after treatment, but their cognitive dysfunction symptoms would persist as residual symptoms. Some scholars considered that cognitive dysfunction in patients with MD was a "phenotype" which existed independently.So, it is very important to study the cognitive dysfunction for patients with MD. Growing evidence has shown that interaction of genetic factors and environmental factors may be involved with the etiology and pathogenesis of MD which is still unclear. Population genetics study has shown the incidence of MD in first-degree relatives of depression propositus was 2 to 3 times higher compared with normal people. Studies on molecular genetics have shown that the HTR3B Polymorphism may be associated with the pathogenesis of depression. Previous research suggests that the HTR3B play a critical role in cognitive process of human in the amygdala, prefrontal cortex and brainstem regions.At present, there is no study on HTR3B polymorphism and cognitive dysfunction of the Han population with MD.Here, we aim to investigate the genetic association between the HTR3B polymorphism and MD, and to explore the critical polymorphism that could influence the cognitive dysfunction in patients in a Chinese Han population.MethodsIn the present case-control study, a total of 240 patients and 232 normal controls were recruited. All The subjects are Chinese Han population, Age 30 to 60 years old, men and women not limited. They volunteered to participate in this study and signed a written informed consent. Patients with MD were diagnosed by using criteria in Diagnostic and Statistical Manual of Mental Disorders, (DSM-IV) and their scores of Hamilton Depression Scale, (HAMD-24) were higher than 20. Control group should not have any mental disorders conform to the diagnosis criteria in DSM-IV.The demographic information of 240 patients with MD and 232 normal controls was gathered by a self-made general information questionnaire. Hamilton Depression Rating Scale for Depression (HAMD) was used to assess the patients’features and the severity of clinical symptoms. Peripheral venous blood samples of all the subjects were taken on the second day. The DNA was extracted with DNA extracton. Sequenom Mass Array of MALDI-TOF was used to detect the SNPs of rs10789980, rs1062613, rs11604247, rs1176722, rs2276302, rs1176719, rs10160548, rs1176713, rs1182457 and rs897685. Hamilton Depression Scale (HAMD) was used to evaluate clinical symptoms of the patients. Cognitive function of the subjects was assessed with cognitive function test battery. Plink 2.0 software was used to test Hardy-Weinberg equilibrium and calculate genotype frequency, allele frequency, odds ratio (OR) and 95% confidence interval (95%CI). Genotype data were imported into the SPSS 20.0 database to analysis the association of SNPs with clinical phenotype and cognitive function in major depressive disorder. All statistical analyses were performed using SPSS20.0. The data were described with mean, median, standard deviation for continuous variables, and frequencies and prportions were used for categorical variables. Two sample independent t-test and one-way analysis of variance tests were used to compare the differences between demographics data of subjects, such as age, gender and degree of education. The comparison of the cognitive test results between the patients and the control was used two sample independent t-test. The frequency of genotype and allele which accord with H-W balance law were described. Person x2 tests and Fisher exact tests were used to compare the difference in requency of genotype and allele between the case-control. Nonparametric tests were used to analyze different genotype and the clinical features of depressive disorder. The correlation of genotypes and cognitive function was performed by covariance analysis. A p value of less than 0.05(2-sided significance testing) was considered statistically significant in all analyses.Results1. Patients’cognitive function, except trail making test, were statistically different from the normal control. This suggests that the cognitive function include Short-term memory, attention and executive function of patients were significantly damaged in patients.2. There were significantly differences in the genotype distribution and allelic frequencies of the rs1176744 and rs2276305 polymorphism between patients and normal controls(P<0.05). The GG(6.3%) and AA(4.2%) genotype frequency in MD group were higher than those in normal group (1.7%,3%). There were significantly differences in the allelic frequencies of the rs1176744 and rs12795805 polymorphism between patients and normal controls(P<0.05). The G(22.9%) and C(18.3%) genotype frequency in MD group were higher than those in normal group(14.1%,13.5%). These two locus mutations were positively correlated with the risk of MD.3. The total score and factor score of HAMD in patients were significantly different among the four genetic groups of rs10789970, rs4938056, rs2276305 and rs12795805; the rs4938056 and rs12795805 polymorphism is a significant influencing factor on the severity of depression symptoms in patients. The rs2276305 polymorphism may be involved with the lighter depressive symptoms.4. Compared the cognitive function of patients with different HTR3B genetypes, we found that the homozygote (CC) in rs10789970 has a worse ability in Words learning test, simple visual test and Stroop color test compared with the homozygote(TT). Our results have shown that for rs4938056 the homozygote(CC) has a lower score than the Homozygote(TT) in Words learning tests and simple visual test and a higher score in the Stroop color-word test. This result illustrates that the homozygote(CC) may has a worse short-term memory as while as a better attention compare to the homozygote(TT). For rs1176744, the homozygote(GG) has a worse ability in Symbol encoding, verbal fluency, breadth positive sequence space compared the patients who carried a T allele. This result stated that the homozygote(GG) may be damaged more in cognitive function such as Executive function, short-term memory and attention. For rsl672717, the homozygote (CC) has a worse ability in Simple words learning test, vision test and the Stroop colour word test compared the homozygote(TT). This result stated that the homozygote(CC) may be damaged more in cognitive function such as short-term memory and attention. For rs2276305, the homozygote(AA) has a worse ability in digital sequence test compared the patients who carried a G allele. This result stated that the homozygote(AA) may have a worse short-term memory.Conclusions1. The cognitive function patients with MD of include Short-term memory; attention and executive function of patients were significantly damaged.2. Our data provides evidence that the rs1176744, rs2276305 and rs12795805 of HTR3B polymorphism may be involved in the etiology of MD in Han Chinese population3. The rs10789970, rs4938056, rs2276305 and rs12795805 polymorphism are associated with depressive symptoms of patients.4. The rs10789970, rs4938056, rs1176744, rs1672717 and rs2276305 polymorphism of HTR3B may be related to short-term memory, attention and executive function in patients with MD. HTR3B polymorphism may be involved with cognitive dysfunction mechanism. Cognitive dysfunction could be considered as an endophenotype which is independent of depressive disorder. |
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